Updates on Seizure Management
Karen Kline, DVM
Seizures are a common problem in small animal veterinary neurology; animals with seizure disorders comprise a large percentage of patients seen in private and referral practices. This discussion will focus on seizure etiology, pathogenesis, diagnostics, and present and future treatment options.
Seizures are described as cerebral dysrhythmias or paroxysmal depolarization shifts whose recurrence is common. Seizures arise in the cerebral cortex. Owners will describe their pets as having fits or convulsions; textbooks will describe seizures as "ictal events". Before seizures are truly called seizures, they must be delineated from "episodes". This delineation is dependent upon a thorough history, physical and neurologic examinations. Episodes that are often mistaken for seizures can include cardiac-related syncopal events, vestibular events, musculoskeletal or neurologic pain, intoxications and vascular accidents.
The differentiation between seizures and the above episodes can be difficult. Seizures are comprised of three components - the aura (pre-ictal phase), the ictus (the actual seizure event) and the post-ictal period. The pre-ictal period may last seconds to days in advance and the patient may seem restless, seek the owner, or display abnormal behavior. The ictal period is the actual seizure itself and may last only seconds up to status epilepticus (non-stop seizure activity). The post -ictal period may last seconds to days and may be comprised of increased appetite, lethargy, visual loss and behavior changes.
Seizures themselves may be focal, partial motor, psychomotor or generalized (major motor, grand mal); the pre-ictal, ictal and post-ictal periods may be variable for each. The ictal period of generalized seizures is characterized by loss of consciousness, purposeless limb movements, and generalized motor dysfunction. Focal motor seizures are usually due to an underlying past or present acquired cause and a change in consciousness is inconsistent. Involuntary movement of the extremities, head or ear twitching, salivation and/or temperature elevations may be observed. Psychomotor or limbic (temporal) lobe seizures can be characterized by fly-biting, tail-chasing, floor-licking or manifestations of GI disturbances.
Seizures may be isolated, occur in clusters or may present as status epilepticus (persistent seizures). All seizures begin with a seizure focus and discharge and an eventual termination after a period of kindling of seizure activity much like a fire with kindling wood. Causes of seizures are multiple and the DAMNIT list of differentials may be used to correlate etiology with signalment and history. Seizure etiology can be divided more specifically into three categories: structural, functional (metabolic) or idiopathic (cryptogenic). Structural causes include inflammation, neoplastic, vascular events, trauma, or congenital anomalies. Functional causes include electrolyte disturbances, hypoglycemia, hepatic encephalopathy or toxicities. When both structural and functional causes have been ruled out, a diagnosis of idiopathic (cryptogenic) seizures is presumed. Post traumatic or infectious agents that have come and gone and are non-progressive may fall into this category. Stereotypic seizures of this type are termed "idiopathic epilepsy" and are characterized by a normal neurologic exam and normal interictal period. Adult or late onset seizures are generally more likely due to a structural cause where as juvenile onset seizures are more likely traumatic, inflammatory, or extracranial in origin (i.e. portosystemic shunt, MVD).
Diagnostics involved in determining seizure etiology depends upon patient history, signalment, physical and neurologic examination findings. A mean data base should include CBC, serum chemistry, UA and pre and post-bile acids. Further diagnostics depending upon above findings and the individual findings of the patient. These may include further diagnostic imaging such as CT scan, MRI, radiographs, blood pressure, endocrine testing , and CSF analysis.
Seizure therapy is based upon choosing the correct drug and allowing the patient a good to excellent quality of life. The criteria for beginning an anticonvulsant are: 1) if seizures occur with a frequency greater than once a month, 2) Status epilepticus 3) Cluster seizures, and 4) owner preference. The goal of seizure therapy is to control but no cure seizures. This should be made clear to the owner.
The emergency management of seizures includes establishing and treating the underlying cause, obtaining pretreatment blood work, treating the hyperthermia that accompanies status epilepticus, and the "ABC's" of emergency medicine (airway establishment, breathing, cardiopulmonary resuscitation. Valium (Diazepam) is the drug of choice for status epilepticus or cluster seizures. It can be used either intravenously or per rectally. The IV dose is 0.25-0.5 mg/kg and the per rectal dose is 0.25-1 mg/kg. The above can be repeated 2 to 3 times. If this therapy fails, phenobarbital or pentobarbital (2-8 mg/kg to effect) can be administered IV. New studies in human medicine indicate that Propofol may be helpful, although studies in dogs are limited. Pentobarbital should be used with caution, since it can cause respiratory depression. Supportive care of the seizure patient includes temperature control, eye lubrication, bladder expression, turning every 2-4 hour and head elevation.
Therapy for recurrent seizures, as mentioned above is aimed at decreasing seizure frequency and severity. The drug of choice has been and still is phenobarbital. It has a broad spectrum, is safe, efficacious, and inexpensive. Its efficacy however is complicated by its induction of hepatic microsomal enzymes which can cause the concentration of the drug to drop by 50% over the first 3 to 6 months of treatment. The dose is 2-4 mg/kg BID. It is recommended to achieve a trough blood level 1 hour before the next dose, but this is debatable. Use of serum separation tubes may falsely lower levels. Normal blood levels should be 15-40 µg/ml and the lowest effective dose should be used to maintain a seizure-free state. The half-life is 36-48 hours and blood levels should be checked in 3 weeks post-institution of therapy. Side effects of phenobarbital include polyuria, polydipsia, pholyphagia, and weight gain. Elevated Alkaline phosphatese (ALP) and ALT are the most common serum chemistry abnormalities. Bone marrow suppression has also been reported. Serum bile acids should be performed on an every 6 month to 1 year basis and if elevated or if undesirable side effects occur, then an alternative anticonvulsant should be used. That alternative is Potassium Bromide (KBr) and is becoming a more commonly prescribed primary anticonvulsant. It is the drug of choice as an adjunctive therapy. Its mechanism of action is not completely understood, but is most likely due to membrane hyperpolarization due to the influx of bromide ions. It is not metabolized by any organ in the body and it excreted through the kidneys. The dose is 100 mg/kg BID for 2 days (loading dose) and 10 mg/kg BID as a maintenance dose. The therapeutic range is 1000-3000 µg/ml. Blood levels should be checked in 1 month post initiation of therapy. It is available in liquid or capsule form. The drug, however, must be compounded and is not currently manufactured commercially. Side effects of KBr include sedation, vomiting, and rarely pancreatitis. Saline diuresis can be used if profound sedation occurs. Benefits of KBr include no hepatic metabolism, the ability to decrease the amount of phenobarbital concurrently used and its inexpensiveness. Other anticonvulsants on the horizon and, now being used, include Gabapentin (Neurontin®) and Felbamate. Other human drugs such as Topamax are being explored as possible alternatives when refractory seizures occur in the absence of concurrent structural disease. Other options for seizure management include dietary management and acupuncture.
The key facts to remember about seizure therapy are that owners must understand that seizures are a treatable, but not curable condition, seizure frequency is unpredictable, correct diagnosis is extremely important and that seizure control is individualized to each patient.